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39
Breast Carcinoma Women Previously Hodgkin Disease
Kathryn L. Cook1 Dorit D. Adler1 Allen S. Lichter2 Debra M. lked& Mark A. Helvie1
The
increased
Hodgkin
risk
disease
of a second
is well
no reports
of the
cancer
There have
been
evaluate AJR
disease.
was
appears
33.5
to be
treated
for Hodgkin disease detection
The
years; an
appropriate
diagnosis
increased
for Hodgkin
July
age was
made
This
in
rare association.
To
cancer
breast
for
is a relatively
in this
group
of women
seven breast cancers
women
at the
10-23
years
of breast
breast
treatment cancer
association
in routine
after of
of the
prevalence
disease.
modifications
155:39-42,
developing
of breast
average
for
development
We report six patients who developed
for Hodgkin
of breast
neoplasm
Subsequent
mammographic
have been published. treatment
malignant
documented.
women who have been treated date,
in Young Treated
time
after
carcinoma
should
cancer
treatment. in women
receive
screening
after
of diagnosis
further
who
study
for these
to
women.
1990
The etiology of breast carcinoma includes genetic and endocrine influences, environmental interactions, and physiologic-immunologic mechanisms. Induction of breast cancer by the effects of radiation has received considerable attention, which is primarily based on statistical analyses of Japanese women subjected to atomic bomb detonations, women who underwent multiple fluoroscopic treatments for tuberculosis, and women who were treated with radiation for postpartum mastitis [1-4]. The association of Hodgkin disease and second malignant neoplasms has been well documented [5-1 6], primarily focusing on the increased prevalence of acute nonlymphocytic leukemia [1 0, 1 3]. Many authors have reported the association of solid malignant lesions developing in patients who had been treated with radiation therapy and/or chemotherapy for Hodgkin disease [5-1 6]. Several case reports have focused on the association between treated Hodgkin disease and breast carcinoma [1 7-20]. The purpose of our study was to evaluate the association between treatment of Hodgkin disease and the development of breast cancer.
Materials
and Methods
In July 1989, 133 women under 40 years of age in whom Hodgkin disease had diagnosed were identified by computer search through the hospital tumor registry. Received October 1 3, 1 989; vision February 1 2, 1990. 1 Department of Radiology, Center Dr., 48109-0326. Adler.
TC 2910, Address
Medical
Center
1500
Dr., Ann Arbor,
Roentgen
Ml 48109.
Ray Society
re-
E. Medical
Oncology,
0361-803X/90/1551-0039 © American
after
Box 0326, Ann reprint requests
of Radiation
2
accepted
Arbor, Ml to D. D. 1500
E.
registry contains some outpatient
a record of all diagnoses data. In addition, all women
seen at the hospital limited
to women
between
younger
age group.
Six such women
diagnosed,
were
found.
January
old because
(seven breast cancers),
A true
have no record of all the women
statistical
The
of tumors in inpatients since 1936 and includes with both Hodgkin disease and breast carcinoma
1936 and July 1989 were identified.
40 years
than
been
analysis
(both inpatient
breast
cancer
in whom
of the
data
and outpatient)
Hodgkin is not
The study was
is relatively
rare in this
disease
possible,
had
because
who had Hodgkin
been we
disease
during this period. The complete hospital records of the six women and mammograms of four of the six were reviewed. The remaining two women did not have mammograms. Limited details of radiotherapy were available for five women. Six women were diagnosed with
COOK
40
Hodgkin known
disease histology;
(three
with
stages
hA
nodular to
IlIB)
sclerosing at an
and three
early
age
(range,
mean, 1 8 years) and received radiotherapy and/or apy. All six underwent mantle radiation (3700-4950 rad Gy]), four had abdominal radiotherapy (3520-4700 rad Gyl), and one woman had 4000 rad (40 Gy) of additional
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
years;
the pelvis. Two of the women received mycin (doxorubicin, Adria Laboratories,
with
un-
10-27
chemother[37.0-49.5 [35.2-47.0
radiation to chemotherapy, MOPP/AdriaDublin, OH) and Velban (yin-
blastine sulfate, Lilly, Indianapolis, IN). Three of the women underwent film/screen mammography (CGR, Senographe 500T, Columbia, MD; Mammex DC Mag, Bayshore, NY) at our hospital. The fourth patient underwent
mammography
for interpretation
elsewhere,
but
the
films
were
submitted
to our hospital.
Results Seven breast cancers, bilateral in one patient, developed in six women when they were 26-38 years old (mean, 33.5 years), an average of 1 7.5 years (range, 1 0-23 years) after the first course of radiotherapy for Hodgkin disease. One woman died of metastatic breast cancer (details unknown) at 36 years old, 27 years after her first treatment for Hodgkin disease. Four women were referred for mammography for abnormal but clinically benign findings. Three of the women found a relatively large palpable breast mass (1 .5, 2.5, 3.0 cm), and
the fourth
patient,
with
bilateral
breast
cancers,
presented
with right nipple retraction. Significantly, this last patient subsequently was diagnosed with a contralateral nonpalpable carcinoma. Two additional women were diagnosed clinically; no mammograms were obtained. Family history for breast carcinoma was negative in three cases, positive in two, and unknown in one. The mammographic density was fatty or mixed in three women and predominantly glandular in one. The mammographic findings were interpreted as highly suggestive of malignancy in all five cancers; two clusters of microcalcifications (Fig. 1) and two spiculated masses (Fig. 2) were among
Fig. 1.-A, Right craniocaudal mammogram in shows cluster of microcalcifications (arrowheads) spiculated density (arrow). B, Magnified (1.5x) right craniocaudal view baftE (arrowhead) and spiculated density (arrow). C, Photographically coned magnified view (right c suggestive nature of microcalcifications (arrowheac needle aspiration findings of palpable mass were p results showed invasive ductal carcinoma with angiot,..,.... abnormalities.
ET AL.
AJR:155, July 1990
the findings. The right nipple retraction in the woman with bilateral breast cancers was associated with a broad area of parenchymal distortion on the mammogram. Three of the cancers
were
in the upper
outer
quadrant,
and the other
five women who subsequently underwent eral in one patient). The complete surgical
logic diagnoses
of the other
two
in
mastectomy (bilathistory and patho-
breast
cancers
are not
available.
All three
palpable
breast
masses
proved
to be invasive
ductal carcinomas, two with angiolymphatic invasion and one with a positive axillary node. The woman with bilateral breast cancers had invasive multifocal lobular carcinoma with angiolymphatic invasion in the right breast, multifocal intraductal carcinoma with foci of invasion in the left breast, and uninvolved bilateral axillary nodes.
Discussion We describe six young women diagnosed with breast carcinoma after curative therapy for Hodgkin disease. In the four women with five cancers who underwent mammography, the mammogram was distinctly abnormal and highly suggestive of malignancy.
This
was
despite
the clinical
impression
that
the three palpable breast masses were benign. In no case was the carcinoma obscured by breast parenchyma despite the relatively young age of the women. In addition, an unsuspected nonpalpable with bilateral breast All of the women
carcinoma was discovered cancers. in our study were younger
old when breast cancer was diagnosed, were younger than 30 years old. Breast group
is very rare, with the reported
29 years
at 8.8/1 00,000
year-old age group, tively low [21].
women
the prevalence
in the woman than 40 years
and two of them cancer in this age
prevalence
[21].
for ages
,
:
.::.t.:4’.
*kA1:
25-
Even in the 30-39-
of breast
cancer
is rela-
..
....
two
were extensive, involving more than one quadrant. Surgical biopsy confirmed the diagnosis of carcinoma
:.
-
BREAST
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
AJR:155, July 1990
CANCER
AND
HODGKIN
DISEASE
41
matopoietic and solid second malignant neoplasms that develop in synergy with radiation and/or chemotherapy. The minimum latent period between radiation exposure and induction of breast carcinoma is reported to vary between 5 and 1 5 years; 1 0-1 5 years after fluoroscopy for tuberculosis, 1 5 years after mastitis treated with radiation, and 5-1 0 years after Japanese atomic bombings [1 3]. Furthermore, the latent period appears to be longer in women younger than 30 years old at the time of radiation exposure and shorter in women older than 30 [1 4]. The mean interval between the first radiation exposure for treatment of Hodgkin disease and the development of breast carcinoma in our six cases is similar to that of three previous case reports [1 7-1 9], in which the interval ranged between 4 and 1 7 years, with an average of 12.6 years. These data are also in keeping with the prolonged induction time of radiationinduced cancer [12]. ,
,
..
Fig. 2.-Right craniocaudal view in 28-year-old woman with palpable mass shows 2-cm spiculated mass (arrows). Pathologic results showed invasive ductal carcinoma with involvement of one of nine axillary nodes.
The association malignant
dressed
of treated
neoplasms,
Hodgkin
including
[5-1 6]. Three published
breast
disease
with second
cancer,
has been
case reports
ad-
focus on the
association between treated Hodgkin disease and breast carcinoma [1 7-1 9]. Other thoracic neoplasms that developed after treatment for Hodgkin disease have been reported. Lung cancer is the most common associated thoracic tumor but esophageal and thyroid cancers and various rare tumors including bone and soft-tissue sarcomas also have been noted [5, 16]. A mediastinal hemangiopericytoma developed in one 34-year-old woman at our institution 9 years after treatment for Hodgkin disease.
The literature radiation in
suggests
exposure
the development
that a patient’s
is one of the most
age at the time of
important
of breast cancer [22-25],
risk factors
primarily
on the
basis of data from the Japanese atomic bomb study, in which women exposed at 1 0-1 9 years old had the greatest risk.
This is also supported by tuberculosis fluoroscopy data and Baral’s study in Sweden [1 3, 26]. Boice et al. [1 ] estimate that the radiation dose to the breasts in women exposed to atomic bomb detonations and ,
in those treated for postpartum mastitis and tuberculosis is between 76-1 21 5 rad (0.76-1 2.1 5 Gy). We do not have estimates of the mean scatter dose to the breasts in our group of women, although the literature suggests that it is approximately 1 38-21 8 rad (1 .38-2.1 8 Gy) for radiotherapy
of breast cancer therapy
and 145-325
of Hodgkin
disease
The relation between
rad (1 .45-3.25
Gy) for radio-
[1 8, 27].
the site of radiation
of the breast after fluoroscopy
this has not otherwise patients with Hodgkin
REFERENCES 1 . Boice JD Jr, Land CE, Shore cancer following low-dose
589-597 2. Shore RE, Hempelmann treated
exposure
and the malignant neo-
location of breast carcinoma or other second plasms is controversial and difficult to study, ports and tumor locations are often not specified, malignant neoplasms have been documented radiation field [5-1 6]. One author, MacKenzie greater proportion of breast cancers in the inner
aspects
Given the relationship between high-dose radiation and subsequent development of breast carcinoma, women who have been irradiated for treatment of Hodgkin disease should be considered at an increased risk for developing breast carcinoma in their lifetime. This problem needs further study because current guidelines for routine screening for breast cancer [28] may not suffice in this group. Perhaps screening should commence approximately 1 0 years after the patient’s first radiation treatment for Hodgkin disease. Two of our patients, ages 26 and 28, were significantly younger than the age at which a baseline mammogram is usually obtained, but mammography clearly delineated the carcinoma in both of them. The other four women, ages 36 to 38, were at the appropriate age for a baseline mammogram, but in retrospect, may have benefited from annual mammography before the age of 40. The association between treated Hodgkin disease and subsequent development of breast cancer has not been previously addressed in the radiologic literature, despite the proved benefits of mammography in screening and diagnosis of breast cancer. We believe that radiologists should be aware of this important association. To evaluate this problem further, we have begun a prospective study-performing screening mammography in asymptomatic young women who have previously been treated for Hodgkin disease.
as radiation and second outside the [4], noted a and central
for tuberculosis,
been documented [27]. disease are predisposed
but
It may be that to many he-
with
X-rays
for
RE, Norman JE, Tokunaga M. Risk of breast radiation exposure. Radiology 1979;131:
LH, Kowaluk E, et al. Breast neoplasms in women acute
postpartum
mastitis.
J Nat!
Cancer
Inst
1977;59:81 3-822 3. Upton AC, Beebe GW, Brown JM, Quimby EH, Shellabarger C. Report of NCI ad hoc working group on the risks associated with mammography in mass screening for the detection of breast carcinomas. J Nat! Cancer Inst 1977;59:481 -493 4. MacKenzie I. Breast cancer following multiple fluoroscopies. 1965;19: 1-8 5. Nelson DF, Cooper 5, Weston MG, Rubin P. Second malignant in patients treated for Hodgkin’s disease with radiotherapy or and chemotherapy. Cancer 1981 48:2386-2393 6. Tucker MA, Coleman CN, Cox RS, varghese A, Rosenberg second cancers after treatment for Hodgkin’s disease. N
Br J Cancer neoplasms radiotherapy SA. Risk of Eng! J Med
COOK
42
1988:318:76-81 7. Tucker
MA, Coleman
apy for Hodgkin’s 8. Arseneau
CN, Rosenberg
SA. Second
cancers
after radiother-
disease. N Eng! J Med 1988;319:244-245
JC, Sponzo
tumors complicating
RW,
Levin
Hodgkin’s
DL, et al. Nonlymphomatous malignant 1972;287: 1119-
disease. N Eng! J Med
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
1122
9. Valagussa P, Santoro A, Fossati-Bellani FF, Banfi A, Bonadonna G. Second acute leukemia and other malignancies following treatment for Hodgkin’s disease. J C!in Oncol 1986;4:830-837 10. Tester WJ, Kinsella TJ, WaIler B, et al. Second malignant neoplasms complicating Hodgkin’s disease: the National Cancer Institute experience. J C!in Onco! 1984;2:762-769 1 1 . Curtis RE, Boice JD Jr. Second cancers after radiotherapy for Hodgkin’s disease. N Eng!J Med 1988;319:244-245
12. Brody RS, Schottenfeld therapy
D, Reid A. Multiple
primary
cancer risk after
for Hodgkin’s
disease. Cancer 1977;40[suppl]: 191 7-1 926 13. Storm HH, Prener A. Second cancer followinglymphatic and hematopoietic cancers in Denmark, 1943-80, Monograph No. 68. Bethesda, MD: National
Cancer Institute, 1985:389-409 14. Kaldor JM, Day NE, Band P. et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin’s disease: an international collaborative study among cancer registries. Int J Cancer 1987;39:571-585
15. Whitelaw DM. Multiple primary carcinomas disease. Can Med Assoc J 1968;99:291-294 16. Lerner H, diagnosed tal. J Surg 17. Carey RW,
associated
with Hodgkin’s
Marcovitz E, Schoenfeld D, Zaren H. Second malignancies in patients receiving chemotherapy at the Pennsylvania HospiOnco! 1983;23:195-197 Linggood RM, Wood W, Blitzer PH. Breast cancer developing
ET AL.
AJR:155,
July 1990
in four women cured of Hodgkin’s disease. Cancer 1984;54:2234-2236 18. Janjan NA, Wilson JF, Gillin M, et al. Mammary carcinoma developing radiotherapy and chemotherapy for Hodgkin’s disease. Cancer
after 1988;
61:252-254 Li FP, Corkery J, Canellos G, Neitlich HW. Breast cancer after Hodgkin’s disease in two sisters. Cancer 1981;47:200-202 20. Zawada W, Stanislaw G. Coexistence of breast cancer and Hodgkin’s disease. Wiad Lek 1975;28:327-329 21 . Cutler Si, Young JL, Connelly RR. Third national cancer survey: incidence data, Monograph No. 41 . Bethesda, MD: National Cancer Institute, 1975: 106-111 22. Land CE, Boice JD Jr, Shore RE, Norman JE, Tokunaga M. Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women. J Nat! Cancer Inst 1980;65:353-376 23. Land CE. Low-dose radiation-a cause of breast cancer? Cancer 1980; 19.
46:868-873
24. Mole RH. The sensitivity
of the human breast to cancer induction
by
ionizing radiation. Br J Radio! 1978;51 :401 -405 25. Feig SA. Biological determinants of radiation-induced human breast cancer. Crit Rev Diagn Imaging 1980;13:229-248 26. Baral E, Larsson LE, Mattsson B. Breast cancer following irradiation of the breast. Cancer 1977;40:2905-2910 27. Basco VE, Coldman AJ, Elwood JM, Young MEJ. Radiation dose and second breast cancer. Br J Cancer 1985;52:319-325 28. American Cancer Society. Prevention-cancer-related checkup guidelines. Prevention-breast cancer: a program of action. In: Cancer Facts and Figures-1989. Atlanta, GA: American Cancer Society, 1989:19-20
39
Breast Carcinoma Women Previously Hodgkin Disease
Kathryn L. Cook1 Dorit D. Adler1 Allen S. Lichter2 Debra M. lked& Mark A. Helvie1
The
increased
Hodgkin
risk
disease
of a second
is well
no reports
of the
cancer
There have
been
evaluate AJR
disease.
was
appears
33.5
to be
treated
for Hodgkin disease detection
The
years; an
appropriate
diagnosis
increased
for Hodgkin
July
age was
made
This
in
rare association.
To
cancer
breast
for
is a relatively
in this
group
of women
seven breast cancers
women
at the
10-23
years
of breast
breast
treatment cancer
association
in routine
after of
of the
prevalence
disease.
modifications
155:39-42,
developing
of breast
average
for
development
We report six patients who developed
for Hodgkin
of breast
neoplasm
Subsequent
mammographic
have been published. treatment
malignant
documented.
women who have been treated date,
in Young Treated
time
after
carcinoma
should
cancer
treatment. in women
receive
screening
after
of diagnosis
further
who
study
for these
to
women.
1990
The etiology of breast carcinoma includes genetic and endocrine influences, environmental interactions, and physiologic-immunologic mechanisms. Induction of breast cancer by the effects of radiation has received considerable attention, which is primarily based on statistical analyses of Japanese women subjected to atomic bomb detonations, women who underwent multiple fluoroscopic treatments for tuberculosis, and women who were treated with radiation for postpartum mastitis [1-4]. The association of Hodgkin disease and second malignant neoplasms has been well documented [5-1 6], primarily focusing on the increased prevalence of acute nonlymphocytic leukemia [1 0, 1 3]. Many authors have reported the association of solid malignant lesions developing in patients who had been treated with radiation therapy and/or chemotherapy for Hodgkin disease [5-1 6]. Several case reports have focused on the association between treated Hodgkin disease and breast carcinoma [1 7-20]. The purpose of our study was to evaluate the association between treatment of Hodgkin disease and the development of breast cancer.
Materials
and Methods
In July 1989, 133 women under 40 years of age in whom Hodgkin disease had diagnosed were identified by computer search through the hospital tumor registry. Received October 1 3, 1 989; vision February 1 2, 1990. 1 Department of Radiology, Center Dr., 48109-0326. Adler.
TC 2910, Address
Medical
Center
1500
Dr., Ann Arbor,
Roentgen
Ml 48109.
Ray Society
re-
E. Medical
Oncology,
0361-803X/90/1551-0039 © American
after
Box 0326, Ann reprint requests
of Radiation
2
accepted
Arbor, Ml to D. D. 1500
E.
registry contains some outpatient
a record of all diagnoses data. In addition, all women
seen at the hospital limited
to women
between
younger
age group.
Six such women
diagnosed,
were
found.
January
old because
(seven breast cancers),
A true
have no record of all the women
statistical
The
of tumors in inpatients since 1936 and includes with both Hodgkin disease and breast carcinoma
1936 and July 1989 were identified.
40 years
than
been
analysis
(both inpatient
breast
cancer
in whom
of the
data
and outpatient)
Hodgkin is not
The study was
is relatively
rare in this
disease
possible,
had
because
who had Hodgkin
been we
disease
during this period. The complete hospital records of the six women and mammograms of four of the six were reviewed. The remaining two women did not have mammograms. Limited details of radiotherapy were available for five women. Six women were diagnosed with
COOK
40
Hodgkin known
disease histology;
(three
with
stages
hA
nodular to
IlIB)
sclerosing at an
and three
early
age
(range,
mean, 1 8 years) and received radiotherapy and/or apy. All six underwent mantle radiation (3700-4950 rad Gy]), four had abdominal radiotherapy (3520-4700 rad Gyl), and one woman had 4000 rad (40 Gy) of additional
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
years;
the pelvis. Two of the women received mycin (doxorubicin, Adria Laboratories,
with
un-
10-27
chemother[37.0-49.5 [35.2-47.0
radiation to chemotherapy, MOPP/AdriaDublin, OH) and Velban (yin-
blastine sulfate, Lilly, Indianapolis, IN). Three of the women underwent film/screen mammography (CGR, Senographe 500T, Columbia, MD; Mammex DC Mag, Bayshore, NY) at our hospital. The fourth patient underwent
mammography
for interpretation
elsewhere,
but
the
films
were
submitted
to our hospital.
Results Seven breast cancers, bilateral in one patient, developed in six women when they were 26-38 years old (mean, 33.5 years), an average of 1 7.5 years (range, 1 0-23 years) after the first course of radiotherapy for Hodgkin disease. One woman died of metastatic breast cancer (details unknown) at 36 years old, 27 years after her first treatment for Hodgkin disease. Four women were referred for mammography for abnormal but clinically benign findings. Three of the women found a relatively large palpable breast mass (1 .5, 2.5, 3.0 cm), and
the fourth
patient,
with
bilateral
breast
cancers,
presented
with right nipple retraction. Significantly, this last patient subsequently was diagnosed with a contralateral nonpalpable carcinoma. Two additional women were diagnosed clinically; no mammograms were obtained. Family history for breast carcinoma was negative in three cases, positive in two, and unknown in one. The mammographic density was fatty or mixed in three women and predominantly glandular in one. The mammographic findings were interpreted as highly suggestive of malignancy in all five cancers; two clusters of microcalcifications (Fig. 1) and two spiculated masses (Fig. 2) were among
Fig. 1.-A, Right craniocaudal mammogram in shows cluster of microcalcifications (arrowheads) spiculated density (arrow). B, Magnified (1.5x) right craniocaudal view baftE (arrowhead) and spiculated density (arrow). C, Photographically coned magnified view (right c suggestive nature of microcalcifications (arrowheac needle aspiration findings of palpable mass were p results showed invasive ductal carcinoma with angiot,..,.... abnormalities.
ET AL.
AJR:155, July 1990
the findings. The right nipple retraction in the woman with bilateral breast cancers was associated with a broad area of parenchymal distortion on the mammogram. Three of the cancers
were
in the upper
outer
quadrant,
and the other
five women who subsequently underwent eral in one patient). The complete surgical
logic diagnoses
of the other
two
in
mastectomy (bilathistory and patho-
breast
cancers
are not
available.
All three
palpable
breast
masses
proved
to be invasive
ductal carcinomas, two with angiolymphatic invasion and one with a positive axillary node. The woman with bilateral breast cancers had invasive multifocal lobular carcinoma with angiolymphatic invasion in the right breast, multifocal intraductal carcinoma with foci of invasion in the left breast, and uninvolved bilateral axillary nodes.
Discussion We describe six young women diagnosed with breast carcinoma after curative therapy for Hodgkin disease. In the four women with five cancers who underwent mammography, the mammogram was distinctly abnormal and highly suggestive of malignancy.
This
was
despite
the clinical
impression
that
the three palpable breast masses were benign. In no case was the carcinoma obscured by breast parenchyma despite the relatively young age of the women. In addition, an unsuspected nonpalpable with bilateral breast All of the women
carcinoma was discovered cancers. in our study were younger
old when breast cancer was diagnosed, were younger than 30 years old. Breast group
is very rare, with the reported
29 years
at 8.8/1 00,000
year-old age group, tively low [21].
women
the prevalence
in the woman than 40 years
and two of them cancer in this age
prevalence
[21].
for ages
,
:
.::.t.:4’.
*kA1:
25-
Even in the 30-39-
of breast
cancer
is rela-
..
....
two
were extensive, involving more than one quadrant. Surgical biopsy confirmed the diagnosis of carcinoma
:.
-
BREAST
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
AJR:155, July 1990
CANCER
AND
HODGKIN
DISEASE
41
matopoietic and solid second malignant neoplasms that develop in synergy with radiation and/or chemotherapy. The minimum latent period between radiation exposure and induction of breast carcinoma is reported to vary between 5 and 1 5 years; 1 0-1 5 years after fluoroscopy for tuberculosis, 1 5 years after mastitis treated with radiation, and 5-1 0 years after Japanese atomic bombings [1 3]. Furthermore, the latent period appears to be longer in women younger than 30 years old at the time of radiation exposure and shorter in women older than 30 [1 4]. The mean interval between the first radiation exposure for treatment of Hodgkin disease and the development of breast carcinoma in our six cases is similar to that of three previous case reports [1 7-1 9], in which the interval ranged between 4 and 1 7 years, with an average of 12.6 years. These data are also in keeping with the prolonged induction time of radiationinduced cancer [12]. ,
,
..
Fig. 2.-Right craniocaudal view in 28-year-old woman with palpable mass shows 2-cm spiculated mass (arrows). Pathologic results showed invasive ductal carcinoma with involvement of one of nine axillary nodes.
The association malignant
dressed
of treated
neoplasms,
Hodgkin
including
[5-1 6]. Three published
breast
disease
with second
cancer,
has been
case reports
ad-
focus on the
association between treated Hodgkin disease and breast carcinoma [1 7-1 9]. Other thoracic neoplasms that developed after treatment for Hodgkin disease have been reported. Lung cancer is the most common associated thoracic tumor but esophageal and thyroid cancers and various rare tumors including bone and soft-tissue sarcomas also have been noted [5, 16]. A mediastinal hemangiopericytoma developed in one 34-year-old woman at our institution 9 years after treatment for Hodgkin disease.
The literature radiation in
suggests
exposure
the development
that a patient’s
is one of the most
age at the time of
important
of breast cancer [22-25],
risk factors
primarily
on the
basis of data from the Japanese atomic bomb study, in which women exposed at 1 0-1 9 years old had the greatest risk.
This is also supported by tuberculosis fluoroscopy data and Baral’s study in Sweden [1 3, 26]. Boice et al. [1 ] estimate that the radiation dose to the breasts in women exposed to atomic bomb detonations and ,
in those treated for postpartum mastitis and tuberculosis is between 76-1 21 5 rad (0.76-1 2.1 5 Gy). We do not have estimates of the mean scatter dose to the breasts in our group of women, although the literature suggests that it is approximately 1 38-21 8 rad (1 .38-2.1 8 Gy) for radiotherapy
of breast cancer therapy
and 145-325
of Hodgkin
disease
The relation between
rad (1 .45-3.25
Gy) for radio-
[1 8, 27].
the site of radiation
of the breast after fluoroscopy
this has not otherwise patients with Hodgkin
REFERENCES 1 . Boice JD Jr, Land CE, Shore cancer following low-dose
589-597 2. Shore RE, Hempelmann treated
exposure
and the malignant neo-
location of breast carcinoma or other second plasms is controversial and difficult to study, ports and tumor locations are often not specified, malignant neoplasms have been documented radiation field [5-1 6]. One author, MacKenzie greater proportion of breast cancers in the inner
aspects
Given the relationship between high-dose radiation and subsequent development of breast carcinoma, women who have been irradiated for treatment of Hodgkin disease should be considered at an increased risk for developing breast carcinoma in their lifetime. This problem needs further study because current guidelines for routine screening for breast cancer [28] may not suffice in this group. Perhaps screening should commence approximately 1 0 years after the patient’s first radiation treatment for Hodgkin disease. Two of our patients, ages 26 and 28, were significantly younger than the age at which a baseline mammogram is usually obtained, but mammography clearly delineated the carcinoma in both of them. The other four women, ages 36 to 38, were at the appropriate age for a baseline mammogram, but in retrospect, may have benefited from annual mammography before the age of 40. The association between treated Hodgkin disease and subsequent development of breast cancer has not been previously addressed in the radiologic literature, despite the proved benefits of mammography in screening and diagnosis of breast cancer. We believe that radiologists should be aware of this important association. To evaluate this problem further, we have begun a prospective study-performing screening mammography in asymptomatic young women who have previously been treated for Hodgkin disease.
as radiation and second outside the [4], noted a and central
for tuberculosis,
been documented [27]. disease are predisposed
but
It may be that to many he-
with
X-rays
for
RE, Norman JE, Tokunaga M. Risk of breast radiation exposure. Radiology 1979;131:
LH, Kowaluk E, et al. Breast neoplasms in women acute
postpartum
mastitis.
J Nat!
Cancer
Inst
1977;59:81 3-822 3. Upton AC, Beebe GW, Brown JM, Quimby EH, Shellabarger C. Report of NCI ad hoc working group on the risks associated with mammography in mass screening for the detection of breast carcinomas. J Nat! Cancer Inst 1977;59:481 -493 4. MacKenzie I. Breast cancer following multiple fluoroscopies. 1965;19: 1-8 5. Nelson DF, Cooper 5, Weston MG, Rubin P. Second malignant in patients treated for Hodgkin’s disease with radiotherapy or and chemotherapy. Cancer 1981 48:2386-2393 6. Tucker MA, Coleman CN, Cox RS, varghese A, Rosenberg second cancers after treatment for Hodgkin’s disease. N
Br J Cancer neoplasms radiotherapy SA. Risk of Eng! J Med
COOK
42
1988:318:76-81 7. Tucker
MA, Coleman
apy for Hodgkin’s 8. Arseneau
CN, Rosenberg
SA. Second
cancers
after radiother-
disease. N Eng! J Med 1988;319:244-245
JC, Sponzo
tumors complicating
RW,
Levin
Hodgkin’s
DL, et al. Nonlymphomatous malignant 1972;287: 1119-
disease. N Eng! J Med
Downloaded from www.ajronline.org by 119.93.237.72 on 11/04/15 from IP address 119.93.237.72. Copyright ARRS. For personal use only; all rights reserved
1122
9. Valagussa P, Santoro A, Fossati-Bellani FF, Banfi A, Bonadonna G. Second acute leukemia and other malignancies following treatment for Hodgkin’s disease. J C!in Oncol 1986;4:830-837 10. Tester WJ, Kinsella TJ, WaIler B, et al. Second malignant neoplasms complicating Hodgkin’s disease: the National Cancer Institute experience. J C!in Onco! 1984;2:762-769 1 1 . Curtis RE, Boice JD Jr. Second cancers after radiotherapy for Hodgkin’s disease. N Eng!J Med 1988;319:244-245
12. Brody RS, Schottenfeld therapy
D, Reid A. Multiple
primary
cancer risk after
for Hodgkin’s
disease. Cancer 1977;40[suppl]: 191 7-1 926 13. Storm HH, Prener A. Second cancer followinglymphatic and hematopoietic cancers in Denmark, 1943-80, Monograph No. 68. Bethesda, MD: National
Cancer Institute, 1985:389-409 14. Kaldor JM, Day NE, Band P. et al. Second malignancies following testicular cancer, ovarian cancer and Hodgkin’s disease: an international collaborative study among cancer registries. Int J Cancer 1987;39:571-585
15. Whitelaw DM. Multiple primary carcinomas disease. Can Med Assoc J 1968;99:291-294 16. Lerner H, diagnosed tal. J Surg 17. Carey RW,
associated
with Hodgkin’s
Marcovitz E, Schoenfeld D, Zaren H. Second malignancies in patients receiving chemotherapy at the Pennsylvania HospiOnco! 1983;23:195-197 Linggood RM, Wood W, Blitzer PH. Breast cancer developing
ET AL.
AJR:155,
July 1990
in four women cured of Hodgkin’s disease. Cancer 1984;54:2234-2236 18. Janjan NA, Wilson JF, Gillin M, et al. Mammary carcinoma developing radiotherapy and chemotherapy for Hodgkin’s disease. Cancer
after 1988;
61:252-254 Li FP, Corkery J, Canellos G, Neitlich HW. Breast cancer after Hodgkin’s disease in two sisters. Cancer 1981;47:200-202 20. Zawada W, Stanislaw G. Coexistence of breast cancer and Hodgkin’s disease. Wiad Lek 1975;28:327-329 21 . Cutler Si, Young JL, Connelly RR. Third national cancer survey: incidence data, Monograph No. 41 . Bethesda, MD: National Cancer Institute, 1975: 106-111 22. Land CE, Boice JD Jr, Shore RE, Norman JE, Tokunaga M. Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women. J Nat! Cancer Inst 1980;65:353-376 23. Land CE. Low-dose radiation-a cause of breast cancer? Cancer 1980; 19.
46:868-873
24. Mole RH. The sensitivity
of the human breast to cancer induction
by
ionizing radiation. Br J Radio! 1978;51 :401 -405 25. Feig SA. Biological determinants of radiation-induced human breast cancer. Crit Rev Diagn Imaging 1980;13:229-248 26. Baral E, Larsson LE, Mattsson B. Breast cancer following irradiation of the breast. Cancer 1977;40:2905-2910 27. Basco VE, Coldman AJ, Elwood JM, Young MEJ. Radiation dose and second breast cancer. Br J Cancer 1985;52:319-325 28. American Cancer Society. Prevention-cancer-related checkup guidelines. Prevention-breast cancer: a program of action. In: Cancer Facts and Figures-1989. Atlanta, GA: American Cancer Society, 1989:19-20
